Alzheimer's discovery hints at drugs to stop cells frying "like eggs"
Scientists at the University of Cambridge have taken cutting-edge sensors used to measure temperature changes within cells to gain fascinating new insights into Alzheimer's disease. The work shows how protein clumps long associated with the condition can cause heat to build up and fry brain cells "like an egg," and more promisingly, demonstrated how drugs could be deployed to stop things from reaching harmful temperatures.
The breakthrough stems from the team's explorations in what's known as intracellular thermogenesis, an emerging field that centers on gauging temperature changes within cells. Advanced sensors have made such measurements possible, and the team is the first to apply it to the study of Alzheimer's disease, focusing their attention on one of the prime suspects in its onset known as amyloid-beta proteins.
The buildup of amyloid-beta proteins into toxic clumps is considered a key driver of the neurodegeneration associated with Alzheimer's disease, and they therefore receive considerable attention from scientists working to better understand the condition. The Cambridge team had been investigating links between intracellular thermogenesis and amyloid-beta aggregation, and these advanced new sensors provided the perfect tools to delve into the details.
“Thermogenesis has been associated with cellular stress, which may promote further aggregation,” said Chyi Wei Chung, the study’s first author. “We believe that when there’s an imbalance in cells, like when the amyloid-beta concentration is slightly too high and it starts to accumulate, cellular temperatures increase.”
The tiny temperature sensors are technically known as fluorescent polymeric thermometers, and the scientists deployed them to study the effects of amyloid-beta on human cell lines in a laboratory setting. As the proteins began to accumulate and form thread-like structures called fibrils, the scientists saw the average temperature of the cells begin to rise, reaching significantly higher levels than cells without any amyloid-beta.
“Overheating a cell is like frying an egg – as it heats up, the proteins start to clump together and become non-functional,” said Kaminski Schierle, who led the research.
And once this aggregation process had begun, the scientists watched it gain momentum, releasing more heat and spreading to nearby cells.
“Once the aggregates have formed, they can exit the cell and be taken up by neighboring cells, infecting healthy amyloid-beta in those cells,” said Chung. “No one has shown this link between temperature and aggregation in live cells before.”
The team says the technique could be used as a way of diagnosing Alzheimer's or screening for drug candidates to treat it. The researchers were able to show that the rise in temperature could be prevented by treating the cells with a drug that inhibits aggregation of the amyloid-beta. While much more research would need to be carried out to translate that into a clinical treatment, the results do indicate the compound has potential as a therapeutic for Alzheimer's disease.
The research was published in the Journal of the American Chemical Society.
Source: University of Cambridge